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Blood, 15 July 2002, Vol. 100, No. 2, pp. 569-577
IMMUNOBIOLOGY
Identification of CD8 +CD11c lineage
phenotype-negative cells in the spleen as committed precursor of
CD8+ dendritic cells
Yong Wang,
Yanyun Zhang,
Hiroyuki Yoneyama,
Nobuyuki Onai,
Taku Sato, and
Kouji Matsushima
From the Department of Molecular Preventive Medicine
and CREST, School of Medicine, The University of Tokyo, Tokyo, Japan.
CD8 + dendritic cells (DCs) represent a functionally
distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of
CD8+ DCs remains to be identified. We reported here that
murine splenic CD8+CD11c lineage phenotype
(Lin) cells could differentiate into CD8+
DCs in vivo after intravenous transplantation. Immunohistochemistry staining showed that donor-derived DCs mainly located in T-cell areas
of the spleen. Functionally, these
CD8+CD11cLin cell-derived
DCs were capable of stimulating allogenic T-cell response, as well as
secreting bioactive interleukin 12 p70 and interferon  . Freshly
isolated CD8+CD11cLin cells
expressed CC chemokine receptor (CCR)2, CCR5, and CCR7 messenger RNA,
whereas CD8+ DCs derived from
CD8+CD11cLin cells further
obtained the expression of CCR6 and macrophage-derived chemokine. Flow
cytometry analysis showed that
CD8+CD11cLin cells were
identified in bone marrow and lymph nodes. Moreover, transplanted
splenic CD8+CD11cLin cells
could also home to thymus and lymph nodes and were capable of
developing into CD8+ DCs in these locations.
However, CD8+CD11cLin
cells failed to differentiate into CD8 DCs, T cells,
natural killer cells, or other myeloid lineage cells in irradiated
chimeras. Taken together, all these findings suggest that
CD8+CD11cLin cells are a
committed precursor of CD8+ DCs.
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